scholarly journals Avoidance and Period-Shortening of Neoadjuvant Chemotherapy Against Triple-Negative Breast Cancer in Stages I and II: Importance of Ki-67 Labeling Index and the Recognition of Apocrine-Type Lesions

2020 ◽  
Vol 19 ◽  
pp. 153303382094324
Author(s):  
Koichi Kubouchi ◽  
Kyosuke Shimada ◽  
Takamichi Yokoe ◽  
Yutaka Tsutsumi

Background: Triple-negative breast cancer encompasses heterogeneous subtypes. Neoadjuvant chemotherapy is ineffective against some triple-negative breast cancers, while others show a favorable prognosis despite chemoresistance. Methods: A total of 51 cases with stages I and II triple-negative breast cancer were analyzed; 34 triple-negative breast cancers treated with neoadjuvant chemotherapy were divided into “good responders” (n = 22), showing therapeutic effect G2b or G3 in surgical specimens, and “poor responders” with therapeutic effect G0, G1a, G1b, and G2a (n = 12). Neoadjuvant chemotherapy was spared in 17 cases (non-neoadjuvant chemotherapy group). Apocrine-type triple-negative breast cancer was defined as triple-negative breast cancer immunoreactive for both androgen receptor and forkhead-box protein A1. Triple-negative breast cancer other than apocrine-type (n = 16) and special types (myoepithelial, medullary, adenoid cystic, and spindle cell carcinomas, n = 6) was categorized as basal-like subtype (n = 29). Prognosis was evaluated in each category. Results: Neoadjuvant chemotherapy provoked significant effects against basal-like triple-negative breast cancer with high Ki-67 labeling (≧50%), and tumor-infiltrating lymphocytes predicted high chemosensitivity. Neoadjuvant chemotherapy was avoidable in triple-negative breast cancer of apocrine- and special types showing low (<50%) Ki-67 labeling. Ten (59%) lesions in the non-neoadjuvant chemotherapy group belonged to the apocrine-type. When clinical complete remission shown by contrast-enhanced magnetic resonance imaging was reached in the course of neoadjuvant chemotherapy against basal-like triple-negative breast cancer, the neoadjuvant chemotherapy period was shortened in 14 (64%) of 22 good responders. Disease-free and overall survival rates were excellent in all groups. Conclusions: The following 2 hypothetical proposals should be proven by large-scale clinical trials. Immunohistochemical recognition of apocrine-type triple-negative breast cancer with low Ki-67 labeling is important for avoiding ineffective/unnecessary neoadjuvant chemotherapy. By employing appropriate clinical imaging, period-shortening is achievable in basal-like triple-negative breast cancer with high Ki-67 labeling.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11539-e11539
Author(s):  
Mashrafi Ahmed ◽  
Tahmina Begum

e11539 Background: Ki-67 is a proliferation marker expressed during cell cycle. ASCO does not recommend this biomarker to be done routinely in breast cancer. As triple negative breast cancer lacks all the ASCO recommended biomarkers (estrogen, progesterone and HER-2 gene), non-recommended markers may carry significant prognostic value in different demographic population. Methods: A retrospective chart review was conducted on patients who were diagnosed with triple negative breast cancer at Saint Joseph Hospital, Chicago from 2005 to 2010. We analyzed the data for Ki67 value among age group, race, menstrual status, tumor histology, stage, treatment given and outcome of the treatment. The data was obtained from medical record, cancer registry and department of pathology. Results: Only 35 cases were found retrospectively. The mean age was 55.6 year. Nearly 47% were African American, 38% White and rest was other races. Most of the cases (71%) were post-menopausal. The average follow-up was 214 days with nearly 62% patients remained disease free, 21% suffered from relapse but alive and 18% died from relapse. The analysis of data is presented here in tabulated form. Conclusions: In our study, we could not reach to statistical significance mostly due to small size of the population. Being a rare subtype of breast cancer, a single center data analysis is not sufficient. This pilot study will encourage us to go for a large scale study involving multi-center or cancer registry data of the state of Illinois. [Table: see text] [Table: see text] [Table: see text] [Table: see text] [Table: see text]


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11519-e11519
Author(s):  
Dimitrios Tryfonopoulos ◽  
Georgios Oikonomopoulos ◽  
Stamatina Demiri ◽  
Lazaros Lekakis ◽  
Nikolaos Fragkiskos Pistamaltzian ◽  
...  

e11519 Background: Triple negative breast cancers are immunohistochemical surrogates of basal-like breast cancers. There is no complete overlap between triple negative and basal-like tumors and as gene expression studies evolve, further subclassification bearing clinical relevance is underway. Our purpose was to correlate clinicopathologic characteristics of triple negative breast cancer tumors with expression of basal markers in an effort to define immunohistochemically subgroups of this heterogenous disease Methods: Data were retrieved and analysed using our electronic databank. Patient samples were reviewed by an expert breast cancer pathologist and stained additionally for EGFR and CK 5/6 antibodies. Results: Sixty-five women with triple negative breast cancer were identified. Mean age was 58.3±12.9 years. Most tumors (86%) were of ductal histology, 53% grade 3, 48% having high Ki-67 index (>14%). 10% of patients presented with Stage IV, 25% with Stage III, 38% with stage II and 27% with stage I disease. 63% of patients were postmenopausal. EGFR staining was present in 43% of tumor samples, whereas CK 5/6 in 38.5%. Both EGFR and CK 5/6 expression was found in 18.5%, whereas 37% of tumors expressed neither EGFR or CK 5/6. No difference was observed between tumors expressing any of these 2 basal markers as compared to EGFR and CK 5/6 negative tumors in terms of Ki-67 index, grade, tumor size and nodal involvement. Lymphovascular invasion and non-ductal histology tended to occur more frequently (p=ns) in non-basal tumors. Additionally, patients with expression of any of the basal markers tended to be more obese than the non-basal triple negative breast cancer patients (p=ns). Conclusions: Further immunohistochemical markers apart from EGFR and CK 5/6 are needed in order to further define clinically meaningful subgroups of triple negative breast cancer.


2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 89-89 ◽  
Author(s):  
Joseph A. Pinto ◽  
Franco F. Doimi ◽  
Justin M. Balko ◽  
Carlos L. Arteaga ◽  
Henry L. Gómez

89 Background: Ki-67 expression in breast cancer has been described as predictive of pathological complete response and prognostic of recurrence free survival (RFS). Our aim was to evaluate in a retrospective cohort of triple negative breast cancer patients if tumor proliferation measured by ki-67 expression is correlated with the outcome. Methods: We evaluated a retrospective cohort of 109 cases of triple negative breast cancer (ER-, PR- and HER2- determined by immunohistochemistry). Ki-67 labeling index was determined in Formalin-Fixed, Paraffin-Embedded residual tumors after neoadjuvant chemotherapy. Patients were stratified in Ki67<15% and Ki67≥15%. Clinicopathological data was retrieved from clinical records. RFS and overall survival (OS) were calculated using the Kaplan–Meier method and variables compared using the log-rank or Breslow test and Hazard Ratios (HR) estimated by the Cox regression. Results: The median age for patients was 47.5 years, 55 (50.5%) were premenopausal and 54 (49.5%) postmenopausal. Eight patients (7.3%) were clinical stages II and 101 (92.7%) stages III. Median of Ki-67 expression was 35.97% (0.96% - 77.7%). There was not association between Ki-67 expression (<15% VS ≥15%) with tumor size, nodal involvement, clinical stage and menopausal status. After a median of follow of 21.6 months, 62 patients (56.9%) have relapsed and 53 (48.6%) have die. The median time for RFS and OS were 21.2 and 31.4 months, respectively. Median of RFS was 12.6 months for Ki67<15% vs 21.2 months for Ki67≥15%, P=0.421 (HR=0.91). Median of OS was 34.9 months for Ki67<15% vs 31.4 months for Ki67≥15%, P=0.755 (HR=1.18). Only nodal involvement was found predictor of shorter RFS (0 nodes, 25.2 months vs 1 -3 nodes, 26.1 months, vs >3 nodes, 9.4 months, P=0.020). Conclusions: Ki-67 labeling index was not related with the outcome in terms of OS and RFS in patients with residual triple negative breast tumors that were treated with neoadjuvant chemotherapy.


Chemotherapy ◽  
2020 ◽  
Vol 65 (3-4) ◽  
pp. 101-109
Author(s):  
Meizhen Zhu ◽  
Yang Yu ◽  
Xiying Shao ◽  
Liang Zhu ◽  
Linbo Wang

<b><i>Background:</i></b> In triple negative breast cancer (TNBC) patients receiving neoadjuvant chemotherapy (NACT), pre-treatment predictors for pathological complete response (pCR) have been reported; however, those for progressive disease (PD) remain unidentified. <b><i>Methods:</i></b> We investigated pre-treatment clinicopathological predictors associated with pCR and PD by retrospectively reviewing data for 165 patients treated between 2015 and 2018. Patients with pCR and PD were compared to those without pCR and PD, respectively, using logistic regression and Kaplan-Meier methods. <b><i>Results:</i></b> Lack of androgen receptor (AR) was an independent predictor of pCR, while high histological grade, low Ki-67 index, and incomplete NACT courses were independent predictors of PD. Mean disease-free survival and overall survival were significantly poorer in PD patients than in pCR patients (15.7, 21.3 vs. 52.4, 56.3 months). <b><i>Conclusions:</i></b> Insights into the chemo-resistance mechanisms and exploration of novel targeted agents in subgroups as per AR and Ki-67 status are needed to improve survival outcomes in TNBC patients.


Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1586
Author(s):  
Milos Holanek ◽  
Iveta Selingerova ◽  
Ondrej Bilek ◽  
Tomas Kazda ◽  
Pavel Fabian ◽  
...  

Pathological complete response (pCR) achievement is undoubtedly the essential goal of neoadjuvant therapy for breast cancer, directly affecting survival endpoints. This retrospective study of 237 triple-negative breast cancer (TNBC) patients with a median follow-up of 36 months evaluated the role of adding platinum salts into standard neoadjuvant chemotherapy (NACT). After the initial four standard NACT cycles, early clinical response (ECR) was assessed and used to identify tumors and patients generally sensitive to NACT. BRCA1/2 mutation, smaller unifocal tumors, and Ki-67 ≥ 65% were independent predictors of ECR. The total pCR rate was 41%, the achievement of pCR was strongly associated with ECR (OR = 15.1, p < 0.001). According to multivariable analysis, the significant benefit of platinum NACT was observed in early responders ≥45 years, Ki-67 ≥ 65% and persisted lymph node involvement regardless of BRCA1/2 status. Early responders with pCR had a longer time to death (HR = 0.28, p < 0.001) and relapse (HR = 0.26, p < 0.001). The pCR was achieved in only 7% of non-responders. However, platinum salts favored non-responders’ survival outcomes without statistical significance. Toxicity was significantly often observed in patients with platinum NACT (p = 0.003) but not for grade 3/4 (p = 0.155). These results based on real-world evidence point to the usability of ECR in NACT management, especially focusing on the benefit of platinum salts.


2021 ◽  
Vol 9 (5) ◽  
pp. 139
Author(s):  
Gines Hernandez-Cortes ◽  
Javier Hornedo ◽  
Raquel Murillo ◽  
Ricardo Sainz De La Cuesta ◽  
Lucia Gonzalez-Cortijo

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 274-274
Author(s):  
E. A. Ibrahim

274 Background: Primary systemic chemotherapy is a standard approach to treating women with locally advanced breast cancers, with higher survival rates reported among patients who attain a pathologic complete response. Triple-negative breast cancer is a special biological entity that remains major challenge to oncologist. Around 12%-20% of breast cancers are triple negative. The current phase II study was conducted to evaluate the pathological complete response (pCR) using cis-platinum containing regimen as neoadjuvant chemotherapy in locally advanced triple negative breast cancer. Methods: Eighteen women with stage III triple negative breast cancer who were recruited between July 2007 and February 2010 at King Fahad Specialist Hospital, Dammam, Saudi Arabia. Neoadjuvant chemotherapy consisted of 4 cycles of AC or FEC 100, followed by 4 cycles consisted of docetaxel-cisplatin every 3 weeks. Primary end point was pathological complete response. Results: Median age: 49 y (24-70); premenopausal: 16; 25% were below 35 years of age; Median tumor size: 9 cm (3.5-19); Grade III: 15; Stage IIIA: 3, IIIB:14, IIIC:1; all but 2 had positive nodes at diagnosis (89%). Clinical evaluation of response by RECIST criteria pre surgery: OR: 17/18 (94%), CR: 9 (50%); PR: 8 (44%).The second sequence with D-Cis-T doubled the rate of clinical CR obtained with AC/FEC. One patient was not operated due to disease progression. Pathological assessment, revealed that 8 (47%) pts had no residual invasive carcinoma in the breast; 3 (18%) had residual occasional scattered tumor cells less than 5 mm (pT1a); 10 (59%) had negative nodes; 8 achieved CpR and 2 nCpR. Patients with residual invasive component and/or nodal involvement had high baseline Ki 67 level. After a median follow up of 24 months, cumulative overall survival at 24 months is 88.9% for whole group. Cumulative overall survival in relation to response was 100% for patients who achieved pCR while overall cumulative survival rate for patients without pCR was 83.3% without statistical significance. Conclusions: This cisplatin based neoadjuvant chemotherapy regimen was well tolerated and achieved a high rate of pCR/npCR.


BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Elie Dagher ◽  
Violette Royer ◽  
Paul Buchet ◽  
Jérôme Abadie ◽  
Delphine Loussouarn ◽  
...  

Abstract Background Invasive mammary carcinomas that spontaneously develop in female cats are associated with high mortality, and resemble the most aggressive human breast cancers, especially triple-negative breast cancer (TNBC). Transcriptome studies showed that TNBCs are a heterogeneous group that includes a potentially hormone-dependent subtype named luminal-AR. Some authors proposed an immunohistochemical definition of the luminal-AR subtype, which is not only positive for Androgen Receptor (AR), but also either positive for the transcription factor Forkhead box A1 (FOXA1), or negative for basal markers. The objectives of this study were to describe AR and FOXA1 expressions in feline mammary carcinomas (FMCs), their prognostic value, and if their coexpression could define a “luminal-AR” subtype of triple-negative mammary carcinomas in cats. Methods In a previously described retrospective cohort of 180 female cats with FMCs, with a 2-year follow-up post-mastectomy, we assessed AR, FOXA1, ER, PR, Ki-67, HER2, and CK14 expressions by automated immunohistochemistry. Results Of the 180 FMCs, 57 (32%) were luminal; i.e., ER and/or PR positive, and 123 (68%) were triple-negative (ER–, PR– and HER2–) FMCs. AR overexpression (found in 33 cases/180, 18%) and FOXA1 index ≥1% (64/180, 36%) were associated with a longer disease-free interval, overall survival, and cancer-specific survival in cats with FMC. Analysis of AR, FOXA1 and CK14 coexpression in triple-negative FMCs showed that AR+ triple-negative FMCs were heterogeneous: there existed an AR+ FOXA1+ CK14– subgroup (n = 7) associated with a better cancer-specific survival by multivariate survival analysis (HR = 0.26, 95% CI: 0.07–0.89, p = 0.03) compared to AR+ FOXA1–CK14+ triple-negative FMCs (n = 46) (HR = 1.00), independently of the pathologic tumor size and pathologic nodal stage. The non-basal-like subtype of triple-negative FMCs that coexpresses AR and FOXA1 (the AR+ FOXA1+ CK14– subgroup) could represent the equivalent of the luminal-AR subgroup of human triple-negative breast cancer. Conclusions We identified an AR+ FOXA1+ CK14– subgroup of triple-negative FMCs that might correspond to the luminal-AR subgroup of human triple-negative breast cancers. Cats with FMC may be interesting spontaneous animal models to investigate new strategies targeting the androgen receptor, especially in the aggressive subtype of AR+ basal-like triple-negative mammary carcinomas with loss of FOXA1 expression (the AR+ FOXA1–CK14+ subgroup).


2014 ◽  
Vol 3 (3) ◽  
pp. 145-52
Author(s):  
Mehrnoosh Etemadi ◽  
Mohammad Mahdi Zamani ◽  
Amir Masoud Nazemi ◽  
Afsaneh Rajabiani ◽  
Alireza Abdollahi

Background: Breast cancer is one of the most frequent malignancies among Iranian women. Triple-negative breast cancer (TNBC) is referred to a type of breast cancer which three biomarkers of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), are negative.Materials and Methods: In this case control study, immunohistopathologic data of patients with TNBC were compared with non-TNBC patients. According to pathological reports, frequency, age, gender, type, size, and tumor grade, involvement and the number of involved lymph nodes, mitosis, Ki-67, necrosis, nuclear grade, tumor side, involvement of the margins, skin involvement, nipple involvement, tumor location, vascular invasion, perineural invasion, presence of in-situ compartment and the benign accompanied tumors, granulomatosis reaction, and calcification were compared between both groups.Results: Two hundred fourteen pathological samples of patients with breast cancer were evaluated. TNBC was seen in about 14% of breast cancers in this study on Iranian population. The mean age of TNBC group was 43±12 years and non-TNBC was 50±12 years (p=0.03). TNBC had significantly higher grade, high mitotic indices, more possibility of P53 positivity and higher level of Ki-67. Presence of vascular and nerve invasion and involvement of the margins at the time of diagnosis were seen in the TNBC group comparing with the non-TNBC group.Conclusion: Younger age, higher grading, neurovascular invasion, P53 positivity, and high levels of Ki-67, lead clinicians to evaluate the biomarkers of TNBC, and in case of confirming TNBC diagnosis, appropriate treatment methods should be added to the routine ones in breast cancer.


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